Strand 1 - Membrane transport and ion channels Flashcards

(120 cards)

1
Q

what do ion channels regulate?

A

membrane potential

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2
Q

what is the membrane potential the difference between?

A

electrical potential/voltage inside and outside of the cell

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3
Q

where does this difference in charge exist in the cell?

A

plasma membrane

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4
Q

what happens to the potential when K+ efflux out of the cell?

A

it gets more negative (as K are positive)

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5
Q

what happens to the potential when Cl- efflux out of the cell?

A

gets more positive

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6
Q

what is a technique used to measure changes in membrane potential?

A

patch clamp electrophysiology

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7
Q

what is the resting membrane potential of most cells?

A

-50 mV

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8
Q

In the Nernst equation what do the letters stand for?

R
T
z
F

A

R = gas constant
T = temp
z = valence of ion (if it’s + or 2+)
F = faraday constant

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9
Q

What is the human homologue of the “shaker” K+ channel?

A

KCNA3

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10
Q

What is gating involving in ion channels?

A

opening/closing in response to stimuli

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11
Q

which animal toxin (puffer fish) is an Na+ blocker?

A

tetradotoxin

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12
Q

which animal toxin (scorpion) is a K+ blocker?

A

charybdotoxin

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13
Q

which animal toxin (funnel web spider) is a Ca2+ blocker?

A

w - agatoxin

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14
Q

what are the polar hydrophillic regions for in ion channels?

A

ligand binding

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15
Q

which two techniques are used to investigate ion channel structure?

A

electron microscopy

x ray crystallography

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16
Q

why are ion channels hard to crystallise?

A

they are large, dyanmic proteins

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17
Q

between which two domains of the 6 transmembrane proteins on an alpha subunit does the pore form?

A

domains 5 and 6

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18
Q

how many domains does a typical K+ channel have?

A

4

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19
Q

what do amino acids occlude at the N terminus of the channel?

what does this cause?

A

the intracellular side of the channel pore

channel inactivation

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20
Q

what happens to the selectivity filter during C type inactivation?

A

conformational change

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21
Q

where does C type inactivation occur?

A

extracellular entrance to channel

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22
Q

what is the difference in transmission in chemical vs electrical synapses?

A

chemical - intermittent transmission

electrical - continuous transmission

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23
Q

a sudden reverse of membrane polarity is also known as an …..

A

action potential

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24
Q

which channels are open during depolarisation?

A

Na+ and K+

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25
Which channels open more slowly in depolarisation?
K+
26
at what voltage is depolarisation?
-55mV
27
which channels are open and then close slowly in repolarisation?
K+
28
which channels are closed in repolarisation?
Na+
29
the voltage gated Na+ channel has 3 states what are they?
Open, closed and inactive
30
are both the Na and K + channels open or closed in hyperpolarisation?
closed
31
what is open during hyperpolarisation?
Na/K pump
32
which channels recover during the relative refractory period?
Na+
33
which channels are still open during the relative refractory period?
K+
34
what does tetradotoxin prevent being fired? in what type of neuron?
action potentials in motor neurons
35
what stage of an action potential does tetradotoxin affect?
depolarisation
36
if a cell cannot repolarise what is the likely cause of this?
voltage gated Na+ channels cannot close
37
what are nociceptors? where in nociceptors, are noxious stimuli transduced to electrical activity?
sensory receptors for painful stimuli at the peripheral terminals
38
where are signals from nociceptors sent to for processing, what must they go through first however?
to the CNS via dorsal root ganglions
39
what are the four stage of nociception?
transduction transmission modulation perception
40
what is transmission achieved by?
primary afferent nociceptors
41
what is modulation achieved by?
interneurons
42
what type of stimuli do AB fibers detect?
non noxious mechanical (light touch)
43
what type of stimuli do Ad fibers detect?
noxious thermal and mechanical
44
what type of stimuli do C fibers detect?
noxious **mechanical, thermal and chemical**
45
which fibers are myelinated? which is more thickly myelinated?
AB, Ad AB more myelinated
46
which fiber is lightly myelinated?
Ad
47
which fiber is not myelinated?
C
48
after primary afferent neurons, where does the signal travel to ?
dorsal root ganglions
49
after dorsal root ganglions where do signals travel to?
the CNS/spinal cord
50
which fiber type has the largest diameter?
AB
51
what is the thermal threshold of type 1 Ad fibers?
53 degrees C
52
what is the thermal threshold of type 2 Ad fibers?
43 degrees C
53
which fiber type has no thermal threshold?
AB
54
What do TRPA1, TRPM8, TRPC5 detect?
noxious cold
55
What do TRPV4, TRPV3, TRPV2, TRPV1 detect?
noxious heat
56
what do chillies contain which binds TRPV1 and gives a sensation of heat?
capsaicin
57
what does menthol bind to to give a cold sensation?
TRPM8
58
Which two TRPs does cannabidiol bind to?
TRPA1, TRPV1
59
where in the body does somatic pain come from?
muscles, joints
60
is somatic pain localised?
yes
61
which 2 types of fibers are responsible for somatic pain?
Ad and C
62
give 3 examples of places where visceral pain can originate from
uterus, kidneys, intestine, liver etc
63
which 2 types of fibers are responsible for visceral pain?
Ad and C
64
is visceral pain responsive to pain relief?
no
65
what are exmples of inflammatory mediators produced from APCs and binds to nociceptors?
TNF alpha, histamine, IL, prostaglandins
66
what type of pain is carpal tunnel syndrome?
neuropathic
67
which stage of nociception is lost due to neuropathic pain?
the first stage - transduction
68
which types of drugs are commonly used to treat neuropathic pain?
opiods, antidepressants
69
which voltage gated ion channel does lidocaine block?
Na+
70
what does lidocaine bind to reversibly?
inner pore of Na+ channel
71
is lidocaine non selective or selective?
non selective
72
does lidocaine have greater affinity for resting or inactive channels?
inactivated
73
which voltage gated Na+ channel subtype is found on the gene SCN9A
1.7
74
what does a channelopathy arise from?
ion channel dysfunction
75
give an example of a genetic channelopathy?
cystic fibrosis
76
is cystic fibrosis monogenic or polygenic?
monogenic
77
what does the dysfunction of Cl- ion influx lead to in the airways in a person with CF?
mucus accumulation
78
Class 1 CFTR mutation is:
failure to create a CFTR from mRNA
79
Class 2 CFTR mutation is:
failure in protein trafficking
80
Class 3 CFTR mutation is:
mutation in ion gating
81
Class 4 CFTR mutation is:
faulty CFTR channel
82
Class 5 CFTR mutation is:
mutation of amount of protein
83
Class 6 CFTR mutation is:
failure to anchor to the plasma membrane
84
autosomal recessive conditions involve both parents to be......
carriers
85
what percentage of children are affected if 2 parents are carriers for an autosomal recessive disease?
25%
86
if one parent is affected by the disease and the other is not, then the condition is ......... ..........
autosomal dominant
87
is autosomal recessive associated with LOF or GOF?
Loss of Function
88
what % of children will be affected if one of their parents is affected by a autosomal dominant disease?
50%
89
which gene is highly expressed by sensory neurons of the DRG?
SCN9A
90
which subunit is associated with the voltage gated Na+ channel subtypes?
alpha
91
which phase of an action potential does NaV 1.7 contribute to ?
rising phase
92
what does Nav 1.7 do subthreshold stimuli?
amplifies them
93
Inherited Erythromelalgia (IEM) is an autosomal ......... condition
autosomal dominant
94
IEM involves burning episodes in which areas of the body?
hands and feet
95
what are attacks triggered by in IEM?
exercise and / or heat
96
when does onset of IEM begin?
childhood
97
which domain does the first mutation (L858H) in IEM occur?
second domain
98
what do mutations in IEM do to the activation threshold? (long process)
- lower it, channels open more easily in response to smaller depolarizations - make the channel activate at more hyperpolarized potentials = prolonged channel opening times
99
Paroxysmal extreme pain disorder (PEPD) is an ................. disorder
autosomal dominant
100
PEPD causes pain in which 3 areas?
rectal, ocular and mandibular
101
what are PEPD attacks triggered by?
chewing and or heat
102
when does PEPD onset occur?
childhood
103
what happens to the threshold for channel activation in PEPD?
it is lowered
104
In PEPD the channel stays open for ...... than usual?
longer
105
CIP is an autosomal ..... condition?
recessive
106
in IEM the L858H mutation means what?
leucine is converted to histidine
107
CIP, IEM, PEPD all have mutations in which gene ?
SCN9A
108
mutations for CIP occur within which two domains?
1 and 2
109
mutations in CIP cause the protein to become.......
truncated
110
Which ions usually contribute most significantly to the resting membrane potential?
Potassium
111
The ____________ pump is an electrogenic ion channel with a stoichiometry of 3:2
sodium/potassium
112
When looking at protein sequence of an ion channel alpha subunit, you would predict that a long stretch of hydrophobic amino acids would be most likely correspond to which domain?
transmembrane
113
regions involved in voltage gating have mainly hydro...... amino acids
hydrophillic
114
alpha subunits of ion channels have 4 homologue domains each with..... transmembrane regions
6
115
how many beta and alpha subunits are in the shaker ion channel?
2 beta, 4 alpha
116
what is continuous transmission in neurons achieved by?
hemichannels
117
charybdotoxin affects which phase of an AP?
repolarisation
118
After an action potential fires, which **ion channel pump **is primarily responsible for returning the cell to **resting** membrane potential?
sodium-potassium pump
119
what does lidocaine prevent the DRG axon from propagating?
an action potential
120
Genetic variation in the SCN9A gene is thought to influence pain perception in humans commonly through ...... in ....... regions
SNPs in coding regions